The overall objective of this proposal is to investigate mucosal strategies resulting in the induction of mucosal and systemic, humoral and cellular immune responses against SIV/HIV. The entire application considers recent advances in novel antigen delivery systems and immunizations routes suitable for mucosal immunization, to effectively stimulate both humoral and cellular arms of the immune response. The proposed studies will be performed by investigators with well-established collaborative tissues and expertise in HIV/SIV virology, pathogenesis, and immunology with emphasis on mucosal immunity. The proposal consists of five inter-related projects: Project 1. Mucosal DNA and Protein Vaccines for AIDS Prevention (Dr. R.W. Compans, P.I., Emory University). Novel DNA vectors and virus-like particles for effective mucosal delivery will be developed to induce mucosal and systemic immune responses; Project 2. Poliovirus Replicons for HIV/SIV Vaccines (Dr. C. Morrow, P.I., UAB). Proposed studies are designed to optimize poliovirus replicons as mucosal vaccine vectors for HIV/SIV antigens; Project 3. Non-human Primate Models for HIV Vaccine Evaluation (Dr. P. Fultz, P.I., UAB). Primate models will be utilized to evaluate the immunogenicity of SIV/HIV antigens provided by investigators involved in Projects 1 & 2 (DNA vectors, virus-like particles, and poliovirus replicons) and given by both mucosal and parenteral routes. Humoral and cellular immune responses in mucosal and systemic immune compartments will be evaluated in collaboration with other participating investigators; Project 4. Novel technologies for Measuring AIDS Virus-Specific CTL in Non-Human Primates (Dr. N. Letvin, P.I.,) Beth Israel Deaconess Medical Center). Primate models will be used to explore virus-specific CTL responses induced by infection and mucosal immunization with antigens generated by investigators in Projects 1 and 2; Project 5. Mucosal Immunization Strategies for Genital Immunity (Dr. J. Mestecky, P.I., UAB)> Immunization strategies that induce mucosal and systemic humoral and cellular immune responses will be investigated in humans with particular emphasis on the immune system of the male genital tract.